An investigation will be undertaken into the possible occurrence of a new group of tetrahydroisoquinoline alkaloids (TIQA) in mammals under conditions of aberrant dopa metabolism. These alkaloids exemplified by norlaudanosolinecarboxylic acid (III) and 1,2-dehydronorlaudanosoline (IV) may be formed in vivo by spontaneous non-enzymatic condensation of 3-4-dihydroxyphenylpyruvic acid (II) and dopamine (I). Rats will be maintained on high daily dosages of dopa with and without inhibitors of enzymes of dopa metabolism and various tissue and excretions will be examined for the occurrence of III, IV, and their catabolites. Similar in vitro studies will be conducted with isolated liver, brain, kidney, and adrenal cortex tissue. If III and IV induce significant inhibition of dopa and dopamine metabolism in vivo, their effect on such specific enzymes as dopa decarboxylase, tyrosine transaminase and tyrosine hydroxylase will be investigated.